We just published our first preprint in bioRxiv: Age-dependence and aging-dependence: The case of neuronal loss and lifespan in a C. elegans model of Parkinson's disease. By Javier Apfeld and Walter Fontana.
The main point of this work is to call attention to untested assumptions regarding the widely-held notion of a “disease of aging”, which is a disease whose incidence is coupled to the aging process. It is notoriously difficult to specify in molecular terms what exactly the aging process consists in, but there is little controversy that it is a determinant of lifespan. To assess whether a process, such as the onset of a disease, might indeed be coupled to aging, requires measuring the joint distribution of lifespan and disease onset to establish at least a correlation between the two. However, this is not possible when the disease is lethal, thereby cutting aging-related lifespan short, as is the case for the major human neurodegenerative diseases.
We resorted to a widely used C. elegans model of Parkinson’s disease, where we can measure the correlation between lifespan determined by aging and neuronal loss because the condition is not fatal. We find no correlation; we even find that both processes can be influenced by a genetic intervention in insulin/IGF1 signaling and yet remain uncorrelated, suggesting some form of compartmentation within the organism. The latter is a finding of specific interest to the worm community, but the overall message is of general concern. Even if the C. elegans model were not to capture a putative connection between Parkinson’s disease and aging in humans, it serves as an eloquent signal that a clear distinction needs to be maintained between age-dependence (which is mere time-dependence) and aging-dependence (which is a dependence on the process that determines lifespan). This distinction is critical to identifying which age-related diseases are likely to show a favourable response to therapies targeting aging. However, should it turn out to be operationally impossible to maintain such a distinction where it matters (e.g. in the human case), then the very concept of a disease of aging is called into question.